The therapeutic value of levodopa, phenobarbital and diphenylhydantoin in the treatment of Parkinsonism, and neurological disorders, respectively, is now well established. Significant amounts of orally administered levodopa are catabolized by the gastric mucosa, never reaching the plasma in the beneficial form, and capable of traversing the blood-brain barrier. It has further been shown in our laboratory that chronic levodopa also induces morphological and cytochemical alterations in the mucosa. In that other orally administered drugs might evoke similar or different responses we propose to investigate the morphological (gross, histological, fine structural), cytochemical (fine structural localization of enzymes), biochemical (cell fractions, protein synthesis, enzyme activities), stereological, autoradiographic and histofluorescence alterations of the gastrointestinal tract following acute and chronic administration of the three drugs. Since most of the drugs also influence the hypothalamo-hypophysial-adrenocortical axis, the adrenal glands, both cortex and medulla, and median eminence will be similarly investigated. The proposed structural-functional studies should provide insight into the existing and potential toxic side effect evoked by chronic therapy with orally administered drugs.